The overall aim of this project is to evaluate the role of prostaglandins in the pathogenesis and treatment of hemorrhagic shock. We are continuing to study the effects of prostaglandin E1 (PGE1) on the redistribution of blood flow to the intestines, pancreas and liver following hemorrhagic shock in the dog. This is being done by means of radioactive microsphere injection. The importance of this work is that decreased flow to the liver might account for the failure of liver function seen following successful resuscitation from hemorrhagic shock. The second aim of the project is to evaluate different dosage schedules for the administration of prostaglandin following hemorrhagic shock. We have shown during the preceding year that there is no diminution of the effect of prostaglandin when given over a period of four hours compared to the previously studied infusion time of 1 hour. This has importance in clinical application of the drug in that it would be necessary to give it for more than 1 hour if its effect were to be maintained through the post-shock period. We propose to give increasing dosages of prostaglandin 5ug and 10ug/kg/min and give adequate fluid to maintain volume and overcome the vasodilitation seen with high-dose prostaglandin and determine if there is a greater increase in cardiac output and fall in systemic and pulmonary vascular resistance with these higher doses. We will also analyze survival following shock with these increased doses. The overall clinical significance of these studies is that shock and post-shock organ failure are still the major cause of death following trauma. Trauma is the leading cause of death among Americans between the ages of 1 and 40.